The behavior of cells in terms of cell-substrate and cell-cell interaction is dramatically affected by topographical characteristics as shape, height, and distance, encountered in their physiological environment. The combination of chemistry and topography of a biomaterial surface influences in turns, important biological responses as inflammatory events at tissue-implant interface, angiogenesis, and differentiation of cells. By disentangling the effect of material chemistry from the topographical one, the possibility of controlling the cell behavior can be provided. In this paper, surfaces with different roughness and morphology were produced by radiofrequency (RF, 13.56 MHz) glow discharges, fed with hexafluoropropylene oxide (C3F6O), in a single process. Coatings with different micro/nanopatterns and the same uppermost chemical composition were produced by combining two plasma deposition processes, with C3F6O and tetrafluoroethylene (C2F4), respectively. The behavior of osteoblast-like cells toward these substrates clearly shows a strict dependence of cell adhesion and proliferation on surface roughness and morphology.